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TNF-α blockage in a mouse model of SCI: Evidence for improved outcome
- Publication Year :
- 2008
-
Abstract
- The aim of our study was to evaluate in vivo the therapeutic efficacy of genetic inhibition of TNF-alpha using TNF-R1 knockout mice in an experimental model of spinal cord trauma. Spinal cord injury was induced by the application of vascular clips to the dura via a four-level T5-T8 laminectomy. To elucidate whether the observed anti-inflammatory status is related to the inhibition of TNF-alpha, we also investigated the effect of infliximab, a TNF-alpha-soluble receptor construct, on spinal cord damage. Pharmacological and genetic TNF-alpha inhibition significantly reduced the degree of (1) spinal cord inflammation and tissue injury (histological score), (2) neutrophil infiltration (evaluated by myeloperoxidase activity), (3) cytokine expression (TNF-alpha), (4) and apoptosis (terminal deoxynucleotidyltransferase-mediated uridine triphosphate end labeling staining, Bax, Bcl-2, and Fas-L expression). In a separate set of experiments, we have also demonstrated that TNF-alpha inhibition significantly ameliorated the recovery of limb function (evaluated by motor recovery score). Taken together, our results demonstrate that inhibition of TNF-alpha reduces the development of inflammation and tissue injury associated with spinal cord trauma, suggesting a possible role of TNF-alpha on the pathogenesis of spinal cord injury.
- Subjects :
- Pathology
medicine.medical_specialty
Fas Ligand Protein
Neutrophils
medicine.medical_treatment
Interleukin-1beta
Models, Neurological
Apoptosis
Inflammation
Critical Care and Intensive Care Medicine
Pathogenesis
Mice
Cytokine expression
Neutrophil infiltration
Trauma
Animals
Antibodies, Monoclonal
Caspase 3
Disease Models, Animal
Infliximab
Mice, Knockout
Proto-Oncogene Proteins c-bcl-2
Receptors, Tumor Necrosis Factor, Type I
Spinal Cord
Spinal Cord Injuries
Tumor Necrosis Factor-alpha
bcl-2-Associated X Protein
Physiology
In vivo
medicine
Spinal cord injury
business.industry
Laminectomy
medicine.disease
Spinal cord
medicine.anatomical_structure
Knockout mouse
Emergency Medicine
Tumor necrosis factor alpha
medicine.symptom
business
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....2c2e133bdac78a38e7c170b25bb68c67